Purpose: The objective of these studies was to compare the effects of glucose and galatose and their respective alcohols, sorbitol and galactitol, on retinal lactate/pyruvate ratios (a surrogate parameter of the cytosolic ratio of free NADH/NAD+) and glycolysis. Methods: Retinas from normal rats were quickly removed and incubated 2 h at 37 C degrees in Krebs-Herpes buffer containing sugars and alcohols as follows: 5 mM glucose + 25 mM galactose, glucose, sorbitol or galactitol. Metabolites were measured by enzymatic methods in extracts of retinas and medium. Results: 25 mM galactose, glucose, and sorbitol (but not galactitol) increased retinal L/P ratios from 22+5 SD in 5 mM glucose to 30+5,, 35+5, and 36+5, respectively(p<0.0001 for each versus 5 mM glucose) and were 23+4 in galactitol. Lactate production was increased by 30 mM glucose (33+3 nmol/ug DNA, versus 26+3 for 5 mM glucose; p<0.0002) but not by galactose (25+3), sorbitol (26+4), or galactitol (24+3). Conclusion: Elevated levels of glucose and of its sugar alcohol both cause a hypoxia-like redox imbalance (e.e., increased retinal lactate/pyruvate ratio) which is associated with increased lactate production by elevated glucose but not by elevated sorbitol levels. Elevated levels of galactose, but not its sugar alcohol, also increase the lactate/pyruvate ratio but without affecting lactate production. These observations are consistent with other evidence which indicates that the hypoxia-like redox imbalances (pseudohypoxia) induced by elevated glucose and galactose levels are mediated by different mechanism(s). This research was supported by NIH grant EY06600. SCIENTIFIC